Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Japan.
Department of Hematology, Toranomon Hospital, Japan.
J Infect Chemother. 2024 Jun;30(6):504-510. doi: 10.1016/j.jiac.2023.12.004. Epub 2023 Dec 12.
This study aimed to identify factors responsible for changes in blood concentrations of a liposomal formulation of amphotericin B (AMPH-B, L-AMB) and analyze the relationships between blood concentrations and efficacy or toxicity.
L-AMB was administered to 30 patients being treated for hematological diseases. AMPH-B plasma concentrations were determined right before the initiation (C) and at the end (C) of infusion on at least 1 day, beginning on Day 3 of L-AMB treatment. The relationships of C divided by dose (C/D ratio) to body weight, age, hepatic function, renal function, serum albumin, C-reactive protein (CRP), response, hypokalemia, and renal impairment were evaluated.
C/D ratio was not correlated with age, hepatic function, renal function, or serum albumin. Body weight adjusted C/D ratio was negatively correlated with CRP. C and C were compared between responders and non-responders, those with or without hypokalemia, and those with or without renal impairment. A higher C in patients with hypokalemia was the only significant difference seen.
The negative correlation between CRP and plasma concentrations was likely caused by higher distribution of L-AMB from the blood to infected tissue in patients with a greater degree of infection, with a resulting decrease in plasma concentrations. AMPH-B plasma concentrations were not related to response. Higher C of AMPH-B were observed in patients with hypokalemia, but no relationship between plasma concentration and renal toxicity was observed, suggesting that AMPH-B plasma concentrations appear to be minimally related to PD when used as L-AMB.
本研究旨在确定导致两性霉素 B 脂质体制剂（AMPH-B，L-AMB）血药浓度变化的因素，并分析血药浓度与疗效或毒性之间的关系。
对 30 例接受血液系统疾病治疗的患者给予 L-AMB。在至少 1 天内，即在 L-AMB 治疗第 3 天开始，在开始（C）和输注结束（C）时测定 AMHB 血浆浓度。评估 C 除以剂量（C/D 比值）与体重、年龄、肝功能、肾功能、血清白蛋白、C 反应蛋白（CRP）、反应、低钾血症和肾功能损害之间的关系。
C/D 比值与年龄、肝功能、肾功能或血清白蛋白无关。体重调整后的 C/D 比值与 CRP 呈负相关。比较了应答者和无应答者、低钾血症患者和无低钾血症患者、肾功能损害患者和无肾功能损害患者的 C 和 C。仅在低钾血症患者中观察到 C 较高，这是唯一的显著差异。
CRP 与血浆浓度之间的负相关可能是由于感染程度较高的患者中 L-AMB 从血液向感染组织的分布增加，导致血浆浓度降低所致。AMPH-B 血浆浓度与反应无关。低钾血症患者的 AMPH-B C 较高，但未观察到血浆浓度与肾毒性之间的关系，表明当用作 L-AMB 时，AMPH-B 血浆浓度似乎与 PD 关系不大。
